The heart expresses the three natriuretic peptide receptors (NPR), namely NPR-A, NPR-B, and NPR-C. We have examined the temporal relationship between the expression of mRNA transcripts for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and their receptors in the heart during the development of cardiac hypertrophy in the aortovenocaval fistula rat. Messenger RNAs were measured by cDNA amplification. Progressive cardiac hypertrophy was accompanied by increased ANP mRNA prevalence throughout the heart and increased BNP mRNA in the left atrium. The most striking observation was the gradual disappearance of NPR-C transcripts (the putative "clearance" receptor) in all chambers; this was in marked contrast to the increase in mRNA levels for NPR-A and NPR-B (the guanylyl cyclase-linked receptors). Our observations have important therapeutic implications if the transcript changes are mirrored at the receptor protein level because (a) the apparent down-regulation of NPR-C may enhance the local action of natriuretic peptides on the heart, and (b) the loss of NPR-C, particularly if it is widespread, may reduce the rate of elimination of the natriuretic peptides, restricting the therapeutic potential of specific NPR-C ligands designed to reduce peptide clearance.
L A Brown, D J Nunez, M R Wilkins
Title and authors | Publication | Year |
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Determinants of natriuretic peptide gene expression
MF McGrath, AJ de Bold |
Peptides | 2005 |
Regulation of guanylyl cyclase/natriuretic peptide receptor-A gene expression
R Garg, KN Pandey |
Peptides | 2005 |
Atrial natriuretic peptide in hypoxia
YF Chen |
Peptides | 2005 |
Cardiac-specific attenuation of natriuretic peptide A receptor activity accentuates adverse cardiac remodeling and mortality in response to pressure overload
JB Patel, ML Valencik, AM Pritchett, JC Burnett, JA McDonald, MM Redfield |
American journal of physiology. Heart and circulatory physiology | 2005 |
Different Effects on Inhibition of Cardiac Hypertrophy in Spontaneously Hypertensive Rats by Monotherapy and Combination Therapy of Adrenergic Receptor Antagonists and/or the Angiotensin II Type 1 Receptor Blocker under Comparable Blood Pressure Reduction
T ASAI, T KUSHIRO, H FUJITA, K KANMATSUSE |
Hypertension Research | 2005 |